1. Field of the invention
This invention relates to derivatives containing a 3- or 4-pyridyl group, namely 3- and 4-pyridylcarbinol esters of adamantanecarboxylic acid and adamantyl 2-(3- and 4-pyridyl)ethyl ketones, together with certain derivatives thereof, their preparation and use in treating prostatic cancer.
2. Description of related art
R. McCague, M. G. Rowlands, S. E. Bartie and J. Houghton, J. Med. Chem. 33, 3050-3055 (1990), have reported that certain esters of 4-pyridylacetic acid, of general formula: ##STR2##
wherein R.sup.a represents a specified alicyclic group (e.g. cyclohexyl or a terpene residue) or ##STR3##
wherein R.sup.b represents a hydrogen atom or a methyl group, inhibit the 17.alpha.-hydroxylase/C.sub.17-20 lyase enzyme complex which is essential for biosynthesis of androgens. The inhibition of androgen biosynthesis by virtue of the hydroxylase/lyase inhibition indicates that the compounds of McCague et al., supra, could be useful for the treatment of prostate cancer since many such tumours depend on androgens for growth.
The compounds of McCague et al. are also inhibitors of aromatase. Aromatase is an enzyme required in the biosynthesis of oestrogens. The ability to inhibit aromatase is considered a desirable property in compounds which are to be used to treat breast cancer. It is undesirable, however, for the treatment of prostatic cancer that a compound should be a strong inhibitor of both aromatase and hydroylase/lyase since the inhibition of aromatase would prevent the removal, by further conversion into oestrogens, of any products of the hydroxylase/lyase enzyme complex which escaped the blockade of hydroxylase/lyase. As a result, a patient could lose some of the benefits of hydroxylase/lyase inhibition. Accordingly, It is desirable to keep the lyase:aromatase inhibition ratio: ##EQU1## as low as possible. (A small numerator indicates that the compound is a powerful inhibitor of lyase. A large denominator indicates that it is a poor inhibitor of aromatase). Further prior art, the relevance of which is apparent only after knowledge of the invention, is referred to below in a separate section.